Modafinil is a wakefulness-promoting agent indicated for use in narcolepsy and idiopathic hypersomnia. It also is used for improving memory and mood. Compared to amphetamines and methylphenidate, modafinil is less likely to cause jitteriness, anxiety, or excess locomotor activity. The precise mechanism of action is not fully understood but it is thought to modulate the central postsynaptic alpha1-adrenergic receptors. However, modafinil has a different pharmacokinetic profile compared to the sympathomimetic agents, such as amphetamines and methylphenidate.
The benzhydrylsulfinyl acetamide structure of modafinil makes it insoluble in water (less than 1 mg/ml) as well as unstable at higher temperatures. These physicochemical properties decrease the drug's potential for abuse via injection or smoking, and lead to reduced cases of dependency compared to amphetamines.
Over the years, more than 40% of the potential candidates in drug discovery and research have failed to emerge as drugs due to their poor biopharmaceutic properties. Most of these are rejected due to poor solubility characteristics and further development is continued only if the new molecule has some marked advantage over the existing molecules indicated for the similar use.
The most common approach used to address the problem of insolubility is by either reducing the drug's particle size or micronizing the drug to the size of a few microns, which increases the effective exposed surface area. Dosage forms which contain micronized drug particles exhibit enhanced solubility and consequently an increase in the bioavailability of the drugs. However, technical and economical problems can arise. For example, highly micronized drug particles possess poor flow properties and an increased chance of re-agglomeration during processing. In some cases, re-agglomeration of micronized drug particles may be so problematic that the basic objective of enhancing the solubility by increasing the effective surface area may be unmet.
U.S. Pat. No. RE 37,516 discloses a method of size reduction and a pharmaceutical composition that has at least 95% of the modafinil particles having a diameter of less than 200 μm.